Skip to content
2000
image of A Human Embryonic Stem Cell-derived Neural Stem Cell Senescence Model Triggered by Oxidative Stress

Abstract

Introduction

Neural stem cells (NSCs) are vulnerable to oxidative stress, which triggers aging and subsequently leads to a reduced regenerative capacity of the central nervous system (CNS). Due to the challenges in acquiring aged human NSCs and the lack of an oxidative stress-induced aging model specifically designed for human NSCs, research related to the aging mechanisms and the screening of anti-aging drugs has been limited. Here, we aimed to establish an oxidative stress-induced senescence model of NSCs by using D-galactose (D-gal).

Methods

Human embryonic stem cells (hESCs) were differentiated into hESC-NSCs using a type I collagen method. hESC-NSCs were characterized by flow cytometry combined with immunofluorescence. A senescence model of hESC-NSCs was established using D-gal and characterized by CCK-8 assay, neurosphere formation, crystal violet staining, DNA damage assay, SA-β-gal staining, and ROS levels measurement. To further explore the profile of gene expression in the D-gal-induced hESC-NSCs senescence model, transcriptome sequencing was performed and analysed by bioinformatics method, followed by verification using qPCR.

Results

The hESC-derived NSCs senescence model demonstrated reduced proliferation and elevated β-galactosidase activity, accompanied by DNA damage, and increased levels of reactive oxygen species. Furthermore, transcriptome analysis unveiled the potential central role of the MAPK signaling pathway in D-gal-induced senescence, involving key genes, including , , , , and .

Conclusion

We presented an oxidative stress-induced senescence model of hESC-NSCs and identified key pathways and genes related to D-gal-induced senescence. Our study might offer an alternative approach to investigating human NSCs aging and provide valuable data for understanding the underlying mechanisms of oxidative stress-induced aging.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/cscr/10.2174/011574888X365639250214045110
2025-04-22
2025-09-01

  • From This Site

    /content/journals/cscr/10.2174/011574888X365639250214045110
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. Audesse A.J. Webb A.E. Mechanisms of enhanced quiescence in neural stem cell aging. Mech. Ageing Dev. 2020 191 111323 10.1016/j.mad.2020.111323 32781077
    [Google Scholar]
  2. Chen F. Liu Y. Wong N.K. Xiao J. So K.F. Oxidative stress in stem cell aging. Cell Transplant. 2017 26 9 1483 1495 10.1177/0963689717735407 29113471
    [Google Scholar]
  3. Escames G. López A. Antonio Garcia J. García L. Acuña-Castroviejo D. Joaquin Garcia J. Carlos Lopez L. The role of mitochondria in brain aging and the effects of melatonin. Curr. Neuropharmacol. 2010 8 3 182 193 10.2174/157015910792246245 21358969
    [Google Scholar]
  4. Hu J. Wang J. From embryonic stem cells to induced pluripotent stem cells—Ready for clinical therapy? Clin. Transplant. 2019 33 6 e13573 10.1111/ctr.13573 31013374
    [Google Scholar]
  5. Carpenter M.K. Inokuma M.S. Denham J. Mujtaba T. Chiu C.P. Rao M.S. Enrichment of neurons and neural precursors from human embryonic stem cells. Exp. Neurol. 2001 172 2 383 397 10.1006/exnr.2001.7832 11716562
    [Google Scholar]
  6. Oh J.H. Jung C.R. Lee M.O. Kim J. Son M.Y. Comparative analysis of human embryonic stem cell‑derived neural stem cells as an in vitro human model. Int. J. Mol. Med. 2018 41 2 783 790 29207026
    [Google Scholar]
  7. Azman K.F. Zakaria R. d-Galactose-induced accelerated aging model: An overview. Biogerontology 2019 20 6 763 782 10.1007/s10522‑019‑09837‑y 31538262
    [Google Scholar]
  8. Zhao C. Chen Z. Liang W. Yang Z. Du Z. Gong S. D-galactose-induced accelerated aging model on auditory cortical neurons by regulating oxidative stress and apoptosis in vitro. J. Nutr. Health Aging 2022 26 1 13 22 10.1007/s12603‑021‑1721‑4 35067698
    [Google Scholar]
  9. Zhou Y. Dong Y. Xu Q. He Y. Tian S. Zhu S. Zhu Y. Dong X. Mussel oligopeptides ameliorate cognition deficit and attenuate brain senescence in d-galactose-induced aging mice. Food Chem. Toxicol. 2013 59 412 420 10.1016/j.fct.2013.06.009 23796539
    [Google Scholar]
  10. Sadigh-Eteghad S. Majdi A. McCann S.K. Mahmoudi J. Vafaee M.S. Macleod M.R. D-galactose-induced brain ageing model: A systematic review and meta-analysis on cognitive outcomes and oxidative stress indices. PLoS One 2017 12 8 e0184122 10.1371/journal.pone.0184122 28854284
    [Google Scholar]
  11. Hu L. Ran J. Wang L. Wu M. Wang Z. Xiao H. Du K. Wang Y. Ginsenoside Rg1 attenuates D‐galactose‐induced neural stem cell senescence via the Sirt1‐Nrf2‐BDNF pathway. Eur. J. Neurosci. 2023 58 9 4084 4101 10.1111/ejn.16147 37753701
    [Google Scholar]
  12. Hu D. Ge Y. Ye L. Xi Y. Chen J. Zhu W. Wang Z. Sun Z. Su Y. Wang D. Xiao S. Qiu J. d ‐Galactose induces the senescence and phenotype switch of corpus cavernosum smooth muscle cells. J. Cell. Physiol. 2024 239 1 e31150 10.1002/jcp.31150 37942832
    [Google Scholar]
  13. Xu X. Shen X. Feng W. Yang D. Jin L. Wang J. Wang M. Ting Z. Xue F. Zhang J. Meng C. Chen R. Zheng X. Du L. Xuan L. Wang Y. Xie T. Huang Z. D-galactose induces senescence of glioblastoma cells through YAP-CDK6 pathway. Aging 2020 12 18 18501 18521 10.18632/aging.103819 32991321
    [Google Scholar]
  14. Xu B. Wang G. Xu L. Ding L. Li S. Han Y. Vitamin C ameliorates D-galactose-induced senescence in HEI-OC1 cells by inhibiting the ROS/NF-κB pathway. Mol. Biol. Rep. 2024 51 1 1157 10.1007/s11033‑024‑10098‑3 39546096
    [Google Scholar]
  15. Liu P. Chen S. Wang Y. Chen X. Guo Y. Liu C. Wang H. Zhao Y. Wu D. Shan Y. Zhang J. Wu C. Li D. Zhang Y. Zhou T. Chen Y. Liu X. Li C. Wang L. Jia B. Liu J. Feng B. Cai J. Pei D. Efficient induction of neural progenitor cells from human ESC/iPSCs on Type I Collagen. Sci. China Life Sci. 2021 64 12 2100 2113 10.1007/s11427‑020‑1897‑0 33740188
    [Google Scholar]
  16. Hartig S.M. Basic image analysis and manipulation in ImageJ. Curr Protoc Mol Biol 2013 14 Unit14.15 10.1002/0471142727.mb1415s102
    [Google Scholar]
  17. Love M.I. Huber W. Anders S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 2014 15 12 550 10.1186/s13059‑014‑0550‑8 25516281
    [Google Scholar]
  18. Ashburner M. Ball C.A. Blake J.A. Botstein D. Butler H. Cherry J.M. Davis A.P. Dolinski K. Dwight S.S. Eppig J.T. Harris M.A. Hill D.P. Issel-Tarver L. Kasarskis A. Lewis S. Matese J.C. Richardson J.E. Ringwald M. Rubin G.M. Sherlock G. The Gene Ontology Consortium Gene ontology: Tool for the unification of biology. Nat. Genet. 2000 25 1 25 29 10.1038/75556 10802651
    [Google Scholar]
  19. Kanehisa M. Furumichi M. Sato Y. Ishiguro-Watanabe M. Tanabe M. KEGG: Integrating viruses and cellular organisms. Nucleic Acids Res. 2021 49 D1 D545 D551 10.1093/nar/gkaa970 33125081
    [Google Scholar]
  20. Mu H. Chen J. Huang W. Huang G. Deng M. Hong S. Ai P. Gao C. Zhou H. OmicShare tools: A zero‐code interactive online platform for biological data analysis and visualization. iMeta 2024 3 5 e228 10.1002/imt2.228 39429881
    [Google Scholar]
  21. Doncheva N.T. Morris J.H. Gorodkin J. Jensen L.J. Cytoscape stringapp: Network analysis and visualization of proteomics data. J. Proteome Res. 2019 18 2 623 632 10.1021/acs.jproteome.8b00702 30450911
    [Google Scholar]
  22. Zhang Y. Ding C. Cai Y. Chen X. Zhao Y. Liu X. Zhang J. Sun S. Liu W. Astilbin ameliorates oxidative stress and apoptosis in D-galactose-induced senescence by regulating the PI3K/Akt/m-TOR signaling pathway in the brains of mice. Int. Immunopharmacol. 2021 99 108035 10.1016/j.intimp.2021.108035 34435579
    [Google Scholar]
  23. Gao Y. Hu Y. Liu Q. Li X. Li X. Kim C.Y. James T.D. Li J. Chen X. Guo Y. Two‐dimensional design strategy to construct smart fluorescent probes for the precise tracking of senescence. Angew. Chem. Int. Ed. 2021 60 19 10756 10765 10.1002/anie.202101278 33624914
    [Google Scholar]
  24. Huang W. Hickson L.J. Eirin A. Kirkland J.L. Lerman L.O. Cellular senescence: The good, the bad and the unknown. Nat. Rev. Nephrol. 2022 18 10 611 627 10.1038/s41581‑022‑00601‑z 35922662
    [Google Scholar]
  25. Di Micco R. Krizhanovsky V. Baker D. d’Adda di Fagagna F. Cellular senescence in ageing: From mechanisms to therapeutic opportunities. Nat. Rev. Mol. Cell Biol. 2021 22 2 75 95 10.1038/s41580‑020‑00314‑w 33328614
    [Google Scholar]
  26. Rufini A. Tucci P. Celardo I. Melino G. Senescence and aging: The critical roles of p53. Oncogene 2013 32 43 5129 5143 10.1038/onc.2012.640 23416979
    [Google Scholar]
  27. Anerillas C. Abdelmohsen K. Gorospe M. Regulation of senescence traits by MAPKs. Geroscience 2020 42 2 397 408 10.1007/s11357‑020‑00183‑3 32300964
    [Google Scholar]
  28. Martin N. Bernard D. Calcium signaling and cellular senescence. Cell Calcium 2018 70 16 23 10.1016/j.ceca.2017.04.001 28410770
    [Google Scholar]
  29. DiMauro T. David G. Ras-induced senescence and its physiological relevance in cancer. Curr. Cancer Drug Targets 2010 10 8 869 876 10.2174/156800910793357998 20718709
    [Google Scholar]
  30. Li S. Xiao J. Huang C. Sun J. Identification and validation of oxidative stress and immune-related hub genes in Alzheimer’s disease through bioinformatics analysis. Sci. Rep. 2023 13 1 657 10.1038/s41598‑023‑27977‑7 36635346
    [Google Scholar]
  31. Papassotiropoulos A. de Quervain D.J.F. Failed drug discovery in psychiatry: Time for human genome-guided solutions. Trends Cogn. Sci. 2015 19 4 183 187 10.1016/j.tics.2015.02.002 25727774
    [Google Scholar]
  32. Liu S. Qiu Y. Xiang R. Huang P. Characterization of H2O2-induced alterations in global transcription of mRNA and lncRNA. Antioxidants 2022 11 3 495 10.3390/antiox11030495 35326145
    [Google Scholar]
  33. Wu Y. Gong Y. Liu Y. Chen F. Chen S. Zhang F. Wang C. Li S. Hu M. Huang R. Guo X. Wang X. Ning Y. Yang L. Comparative analysis of differentially expressed genes in chondrocytes from rats exposed to low selenium and T-2 toxin. Biol. Trace Elem. Res. 2024 202 3 1020 1030 10.1007/s12011‑023‑03725‑w 37326932
    [Google Scholar]
  34. Liang D. Ma X. Zhong X. Zhou Y. Chen W. He X. Integration of host gene regulation and oral microbiome reveals the influences of smoking during the development of oral squamous cell carcinoma. Front. Oncol. 2024 14 1409623 10.3389/fonc.2024.1409623 39474111
    [Google Scholar]
  35. Koloko Ngassie M.L. Drake L.Y. Roos B.B. Koenig-Kappes A. Pabelick C.M. Gosens R. Brandsma C.A. Burgess J.K. Prakash Y.S. Endoplasmic reticulum stress-induced senescence in human lung fibroblasts. Am. J. Physiol. Lung Cell. Mol. Physiol. 2024 327 1 L126 L139 10.1152/ajplung.00264.2023 38771153
    [Google Scholar]
  36. Uddin M.S. Yu W.S. Lim L.W. Exploring ER stress response in cellular aging and neuroinflammation in Alzheimer’s disease. Ageing Res. Rev. 2021 70 101417 10.1016/j.arr.2021.101417 34339860
    [Google Scholar]
  37. Salama R. Sadaie M. Hoare M. Narita M. Cellular senescence and its effector programs. Genes Dev. 2014 28 2 99 114 10.1101/gad.235184.113 24449267
    [Google Scholar]
  38. Yan X. Wang D. Ning Z. Meng Z. Lenvatinib inhibits intrahepatic cholangiocarcinoma via Gadd45a-mediated cell cycle arrest. Discov. Oncol. 2023 14 1 26 10.1007/s12672‑023‑00631‑4 36821012
    [Google Scholar]
  39. Zhu L. Dong C. Sun C. Ma R. Yang D. Zhu H. Xu J. Rejuvenation of MPTP-induced human neural precursor cell senescence by activating autophagy. Biochem. Biophys. Res. Commun. 2015 464 2 526 533 10.1016/j.bbrc.2015.06.174 26159917
    [Google Scholar]
  40. Dong C-M. Wang X-L. Wang G-M. Zhang W-J. Zhu L. Gao S. Yang D-J. Qin Y. Liang Q-J. Chen Y-L. Deng H-T. Ning K. Liang A-B. Gao Z-L. Xu J. A stress-induced cellular aging model with postnatal neural stem cells. Cell Death Dis. 2014 5 3 e1116 10.1038/cddis.2014.82 24625975
    [Google Scholar]
  41. Daniele S. Da Pozzo E. Iofrida C. Martini C. Human neural stem cell aging is counteracted by α-glycerylphosphorylethanolamine. ACS Chem. Neurosci. 2016 7 7 952 963 10.1021/acschemneuro.6b00078 27168476
    [Google Scholar]
  42. Chen P. Chen F. Lei J. Li Q. Zhou B. Activation of the miR-34a-mediated SIRT1/mTOR signaling pathway by urolithin A attenuates d-galactose-induced brain aging in mice. Neurotherapeutics 2019 16 4 1269 1282 10.1007/s13311‑019‑00753‑0 31420820
    [Google Scholar]
  43. Qian J. Wang X. Cao J. Zhang W. Lu C. Chen X. Dihydromyricetin attenuates D-galactose-induced brain aging of mice via inhibiting oxidative stress and neuroinflammation. Neurosci. Lett. 2021 756 135963 10.1016/j.neulet.2021.135963 34022267
    [Google Scholar]
  44. Nam S.M. Seo M. Seo J.S. Rhim H. Nahm S.S. Cho I.H. Chang B.J. Kim H.J. Choi S.H. Nah S.Y. Ascorbic acid mitigates D-galactose-induced brain aging by increasing hippocampal neurogenesis and improving memory function. Nutrients 2019 11 1 176 10.3390/nu11010176 30650605
    [Google Scholar]
  45. Tian S. Zhao H. Guo H. Feng W. Jiang C. Jiang Y. Propolis ethanolic extract attenuates D-gal-induced C2C12 cell injury by modulating Nrf2/HO-1 and p38/p53 signaling pathways. Int. J. Mol. Sci. 2023 24 7 6408 10.3390/ijms24076408 37047379
    [Google Scholar]
  46. Zhang Y. Ni X. Wei L. Yu Y. Zhu B. Bai Y. Pei X. Gao F. Guo L. Yong Z. Zhao W. METTL3 alleviates D-gal-induced renal tubular epithelial cellular senescence via promoting miR-181a maturation. Mech. Ageing Dev. 2023 210 111774 10.1016/j.mad.2022.111774 36608773
    [Google Scholar]
  47. Zhang D. Chen Y. Xu X. Xiang H. Shi Y. Gao Y. Wang X. Jiang X. Li N. Pan J. Autophagy inhibits the mesenchymal stem cell aging induced by D‐galactose through ROS/JNK/p38 signalling. Clin. Exp. Pharmacol. Physiol. 2020 47 3 466 477 10.1111/1440‑1681.13207 31675454
    [Google Scholar]
  48. Shwe T. Pratchayasakul W. Chattipakorn N. Chattipakorn S.C. Role of D-galactose-induced brain aging and its potential used for therapeutic interventions. Exp. Gerontol. 2018 101 13 36 10.1016/j.exger.2017.10.029 29129736
    [Google Scholar]
  49. Shi Z. Geng Y. Liu J. Zhang H. Zhou L. Lin Q. Yu J. Zhang K. Liu J. Gao X. Zhang C. Yao Y. Zhang C. Sun Y.E. Single-cell transcriptomics reveals gene signatures and alterations associated with aging in distinct neural stem/progenitor cell subpopulations. Protein Cell 2018 9 4 351 364 28748452
    [Google Scholar]
  50. Apostolopoulou M. Kiehl T.R. Winter M. Cardenas De La Hoz E. Boles N.C. Bjornsson C.S. Zuloaga K.L. Goderie S.K. Wang Y. Cohen A.R. Temple S. Non-monotonic changes in progenitor cell behavior and gene expression during aging of the adult V-SVZ neural stem cell niche. Stem Cell Reports 2017 9 6 1931 1947 10.1016/j.stemcr.2017.10.005 29129683
    [Google Scholar]
  51. Zhu H. Blake S. Kusuma F.K. Pearson R.B. Kang J. Chan K.T. Oncogene-induced senescence: From biology to therapy. Mech. Ageing Dev. 2020 187 111229 10.1016/j.mad.2020.111229 32171687
    [Google Scholar]
  52. Malumbres M. Pérez De Castro I. Hernández M.I. Jiménez M. Corral T. Pellicer A. Cellular response to oncogenic ras involves induction of the Cdk4 and Cdk6 inhibitor p15(INK4b). Mol. Cell. Biol. 2000 20 8 2915 2925 10.1128/MCB.20.8.2915‑2925.2000 10733595
    [Google Scholar]
  53. Coppé J.P. Patil C.K. Rodier F. Sun Y. Muñoz D.P. Goldstein J. Nelson P.S. Desprez P.Y. Campisi J. Senescence-associated secretory phenotypes reveal cell-nonautonomous functions of oncogenic RAS and the p53 tumor suppressor. PLoS Biol. 2008 6 12 e301 10.1371/journal.pbio.0060301 19053174
    [Google Scholar]
  54. Bahar M.E. Kim H.J. Kim D.R. Targeting the RAS/RAF/MAPK pathway for cancer therapy: From mechanism to clinical studies. Signal Transduct. Target. Ther. 2023 8 1 455 10.1038/s41392‑023‑01705‑z 38105263
    [Google Scholar]
  55. Wang B. Han J. Elisseeff J.H. Demaria M. The senescence-associated secretory phenotype and its physiological and pathological implications. Nat. Rev. Mol. Cell Biol. 2024 25 12 958 978 10.1038/s41580‑024‑00727‑x 38654098
    [Google Scholar]
  56. Xu Y. Li N. Xiang R. Sun P. Emerging roles of the p38 MAPK and PI3K/AKT/mTOR pathways in oncogene-induced senescence. Trends Biochem. Sci. 2014 39 6 268 276 10.1016/j.tibs.2014.04.004 24818748
    [Google Scholar]
  57. Moreno-Cugnon L. Arrizabalaga O. Llarena I. Matheu A. Elevated p38MAPK activity promotes neural stem cell aging. Aging 2020 12 7 6030 6036 10.18632/aging.102994 32243258
    [Google Scholar]
  58. Cortez I. Bulavin D. V. Wu P. McGrath E. L. Cunningham K. A. Wakamiya M. Papaconstantinou J. Dineley K. T. Aged dominant negative p38α MAPK mice are resistant to age-dependent decline in adult-neurogenesis and context discrimination fear conditioning. Behav Brain Res 2017 322 Pt B 212 222 10.1016/j.bbr.2016.10.023
    [Google Scholar]
  59. Rayess H. Wang M.B. Srivatsan E.S. Cellular senescence and tumor suppressor gene p16. Int. J. Cancer 2012 130 8 1715 1725 10.1002/ijc.27316 22025288
    [Google Scholar]
  60. Moskalev A.A. Smit-McBride Z. Shaposhnikov M.V. Plyusnina E.N. Zhavoronkov A. Budovsky A. Tacutu R. Fraifeld V.E. Gadd45 proteins: Relevance to aging, longevity and age-related pathologies. Ageing Res. Rev. 2012 11 1 51 66 10.1016/j.arr.2011.09.003 21986581
    [Google Scholar]
  61. Liu Y. Peng L. Chen J. Chen L. Wu Y. Cheng M. Chen M. Ye X. Jin Y. EIF5A2 specifically regulates the transcription of aging-related genes in human neuroblastoma cells. BMC Geriatr. 2023 23 1 83 10.1186/s12877‑023‑03793‑6 36750933
    [Google Scholar]
  62. Wodrich A.P.K. Scott A.W. Shukla A.K. Harris B.T. Giniger E. The unfolded protein responses in health, aging, and neurodegeneration: Recent advances and future considerations. Front. Mol. Neurosci. 2022 15 831116 10.3389/fnmol.2022.831116 35283733
    [Google Scholar]
  63. Nemetski S.M. Gardner L.B. Hypoxic regulation of Id-1 and activation of the unfolded protein response are aberrant in neuroblastoma. J. Biol. Chem. 2007 282 1 240 248 10.1074/jbc.M607275200 17102133
    [Google Scholar]
  64. Chen C. Dudenhausen E.E. Pan Y.X. Zhong C. Kilberg M.S. Human CCAAT/enhancer-binding protein beta gene expression is activated by endoplasmic reticulum stress through an unfolded protein response element downstream of the protein coding sequence. J. Biol. Chem. 2004 279 27 27948 27956 10.1074/jbc.M313920200 15102854
    [Google Scholar]
  65. Matos L. Gouveia A.M. Almeida H. ER stress response in human cellular models of senescence. J. Gerontol. A Biol. Sci. Med. Sci. 2015 70 8 924 935 10.1093/gerona/glu129 25149687
    [Google Scholar]
  66. Jacob K. Quang-Khuong D.A. Jones D.T.W. Witt H. Lambert S. Albrecht S. Witt O. Vezina C. Shirinian M. Faury D. Garami M. Hauser P. Klekner A. Bognar L. Farmer J.P. Montes J.L. Atkinson J. Hawkins C. Korshunov A. Collins V.P. Pfister S.M. Tabori U. Jabado N. Genetic aberrations leading to MAPK pathway activation mediate oncogene-induced senescence in sporadic pilocytic astrocytomas. Clin. Cancer Res. 2011 17 14 4650 4660 10.1158/1078‑0432.CCR‑11‑0127 21610151
    [Google Scholar]
  67. Wu D. Tan H. Su W. Cheng D. Wang G. Wang J. Ma D.A. Dong G.M. Sun P. MZF1 mediates oncogene-induced senescence by promoting the transcription of p16INK4A. Oncogene 2022 41 3 414 426 10.1038/s41388‑021‑02110‑y 34773072
    [Google Scholar]
  68. Salotti J. Johnson P.F. Regulation of senescence and the SASP by the transcription factor C/EBPβ. Exp. Gerontol. 2019 128 110752 10.1016/j.exger.2019.110752 31648009
    [Google Scholar]
  69. Montes M. Lubas M. Arendrup F.S. Mentz B. Rohatgi N. Tumas S. Harder L.M. Skanderup A.J. Andersen J.S. Lund A.H. The long non-coding RNA MIR31HG regulates the senescence associated secretory phenotype. Nat. Commun. 2021 12 1 2459 10.1038/s41467‑021‑22746‑4 33911076
    [Google Scholar]
  70. Martínez-Zamudio R.I. Roux P.F. de Freitas J.A.N.L.F. Robinson L. Doré G. Sun B. Belenki D. Milanovic M. Herbig U. Schmitt C.A. Gil J. Bischof O. AP-1 imprints a reversible transcriptional programme of senescent cells. Nat. Cell Biol. 2020 22 7 842 855 10.1038/s41556‑020‑0529‑5 32514071
    [Google Scholar]
  71. Chong W. Shastri M. Eri R. Endoplasmic reticulum stress and oxidative stress: A vicious nexus implicated in bowel disease pathophysiology. Int. J. Mol. Sci. 2017 18 4 771 10.3390/ijms18040771 28379196
    [Google Scholar]
  72. Cao S.S. Kaufman R.J. Endoplasmic reticulum stress and oxidative stress in cell fate decision and human disease. Antioxid. Redox Signal. 2014 21 3 396 413 10.1089/ars.2014.5851 24702237
    [Google Scholar]
  73. Liu X. Huang Z. Zhang Y. Shui X. Liu F. Wu Z. Xu S. Lacidipine ameliorates the endothelial senescence and inflammatory injury through CXCR7/P38/C/EBP-β signaling pathway. Front. Cardiovasc. Med. 2021 8 692540 10.3389/fcvm.2021.692540 34295928
    [Google Scholar]
  74. Guindi C. Cloutier A. Gaudreau S. Zerif E. McDonald P.P. Tatsiy O. Asselin C. Dupuis G. Gris D. Amrani A. Role of the p38 MAPK/C/EBPβ pathway in the regulation of phenotype and IL-10 and IL-12 production by tolerogenic bone marrow-derived dendritic cells. Cells 2018 7 12 256 10.3390/cells7120256 30544623
    [Google Scholar]
  75. Maytin E.V. Ubeda M. Lin J.C. Habener J.F. Stress-inducible transcription factor CHOP/gadd153 induces apoptosis in mammalian cells via p38 kinase-dependent and -independent mechanisms. Exp. Cell Res. 2001 267 2 193 204 10.1006/excr.2001.5248 11426938
    [Google Scholar]
  76. Tan H.K. Muhammad T.S.T. Tan M.L. 14-Deoxy-11,12-didehydroandrographolide induces DDIT3-dependent endoplasmic reticulum stress-mediated autophagy in T-47D breast carcinoma cells. Toxicol. Appl. Pharmacol. 2016 300 55 69 10.1016/j.taap.2016.03.017 27049118
    [Google Scholar]
  77. Han N. Yuan F. Xian P. Liu N. Liu J. Zhang H. Zhang H. Yao K. Yuan G. GADD45a mediated cell cycle inhibition is regulated By P53 in bladder cancer. OncoTargets Ther. 2019 12 7591 7599 10.2147/OTT.S222223 31571910
    [Google Scholar]
  78. Okazawa H. Estus S. The JNK/c-Jun cascade and Alzheimer’s disease. Am. J. Alzheimers Dis. Other Demen. 2002 17 2 79 88 10.1177/153331750201700209 11954673
    [Google Scholar]
/content/journals/cscr/10.2174/011574888X365639250214045110
Loading
A Human Embryonic Stem Cell-derived Neural Stem Cell Senescence Model Triggered by Oxidative Stress
Bentham Science Publishers ; https://doi.org/10.2174/011574888X365639250214045110
/content/journals/cscr/10.2174/011574888X365639250214045110
/content/journals/cscr/10.2174/011574888X365639250214045110
Loading

Data & Media loading...


  • Article Type:     Research Article
Keywords: oxidative stress ; neural stem cell ; D-galactose ; Human embryonic stem cell ; transcriptome sequencing ; senescence

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test